Isolated pancreatic rat islets can not be used as an in vitro model to study mechanisms of pancreatic polypeptide (PP) secretion since currently available antibodies do not cross-react appreciably with rodent PP. Therefore, a new in vitro model system has been developed employing aggregates (pseudoislets) of canine endocrine cells prepared by rotational tissue culture of pancreatic single cells obtained by enzymatic dispersion. The goals of the proposed research are two-fold. First, to more thoroughly characterize this new in vitro model by histochemical, functional and biochemical techniques regarding its applicability to the study of PP secretory and biosynthetic mechanisms. Secondly, to elucidate factors and mechanisms controlling PP secretion. Specfic areas of study to be evaluated are: (1) a variety of stimulatory and inhibitory agents known the alter PP release in vivo; (2) the dynamic nature of PP secretion; (3) role of ions and cyclic nucleotides in the release process; (4) interrelationship of PP secretion with the release of insulin and glucagon. These studies will provide important information regarding those forces responsible for inducing PP secretion and will enable us to better desing studies elucidating the physiologic significance of this newly discovered hormone.